Märit Halmin, MD; Klaus Rostgaard, MSc; Brian K. Lee, PhD; Agneta Wikman, MD, PhD; Rut Norda, MD, PhD; Kaspar René Nielsen, MD, PhD; Ole B. Pedersen, MD, PhD; Jacob Holmqvist, MD; Henrik Hjalgrim, MD, DrMedSci; Gustaf Edgren, MD, PhD
Acknowledgment: The authors are greatly indebted to all the blood banks in Sweden and Denmark for both collecting and contributing data to this study.
Grant Support: The assembly of the SCANDAT2 database and the conduct of this study were made possible through grants from the Swedish Research Council (2011-30405, 2007-7469), the Swedish Heart–Lung Foundation (20090710), the Swedish Society for Medical Research (to Dr. Edgren), the Strategic Research Program in Epidemiology at Karolinska Institutet (to Dr. Edgren), and the Danish Council for Independent Research (2009B026).
Disclosures: Dr. Hjalgrim reports grants from the Danish Council for Independent Research for construction of the SCANDAT database and from the Nordic Cancer Union, outside the submitted work. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-1415.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Edgren (e-mail, email@example.com).
Requests for Single Reprints: Märit Halmin, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Halmin and Edgren: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Mr. Rostgaard: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
Dr. Lee: Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, PA 19104.
Dr. Wikman: Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, C2:66 Huddinge SE-14186, Sweden.
Dr. Norda: Klinisk immunologi och transfusionsmedicin Akademiska sjukhuset, 75185 Uppsala, Sweden.
Dr. Nielsen: Department of Clinical Immunology, Aalborg University Hospital, 9000 Aalborg, Denmark.
Dr. Pedersen: Department of Clinical Immunology, Næstved Sygehus, 4700 Næstved, Denmark.
Dr. Holmqvist: AnOpIVA, Centralsjukhuset, 651 85 Karlstad, Sweden.
Dr. Hjalgrim: Afdeling for Epidemiologisk Forskning, Sektor for Epidemiologi og Smitteberedskab, Artillerivej 5, DK-2300 København S, Denmark.
Author Contributions: Conception and design: M. Halmin, K.R. Nielsen, J. Holmqvist, G. Edgren.
Analysis and interpretation of the data: M. Halmin, B.K. Lee, A. Wikman, R. Norda, K.R. Nielsen, O.B. Pedersen, J. Holmqvist, G. Edgren.
Drafting of the article: M. Halmin, B.K. Lee, A. Wikman, R. Norda, K.R. Nielsen, J. Holmqvist, G. Edgren.
Critical revision for important intellectual content: M. Halmin, K. Rostgaard, B.K. Lee, A. Wikman, K.R. Nielsen, O.B. Pedersen, J. Holmqvist, H. Hjalgrim, G. Edgren.
Final approval of the article: M. Halmin, K. Rostgaard, B.K. Lee, A. Wikman, R. Norda, K.R. Nielsen, O.B. Pedersen, J. Holmqvist, H. Hjalgrim, G. Edgren.
Provision of study materials or patients: G. Edgren.
Statistical expertise: K. Rostgaard, B.K. Lee, G. Edgren.
Obtaining of funding: H. Hjalgrim, G. Edgren.
Administrative, technical, or logistic support: M. Halmin, A. Wikman, J. Holmqvist, H. Hjalgrim, G. Edgren.
Collection and assembly of data: M. Halmin, K. Rostgaard, A. Wikman, R. Norda, K.R. Nielsen, O.B. Pedersen, J. Holmqvist, H. Hjalgrim, G. Edgren.
Halmin M, Rostgaard K, Lee BK, Wikman A, Norda R, Nielsen KR, et al. Length of Storage of Red Blood Cells and Patient Survival After Blood Transfusion: A Binational Cohort Study. Ann Intern Med. [Epub ahead of print 20 December 2016]:. doi: 10.7326/M16-1415
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Published: Ann Intern Med. 2016.
Possible negative effects, including increased mortality, among persons who receive stored red blood cells (RBCs) have recently garnered considerable attention. Despite many studies, including 4 randomized trials, no consensus exists.
To study the association between the length of RBC storage and mortality in a large population-based cohort of patients who received transfusions, allowing detection of small yet clinically significant effects.
Binational cohort study.
All transfusion recipients in Sweden and Denmark.
854 862 adult patients who received transfusions from 2003 to 2012.
Patients were followed from first blood transfusion. Relative and absolute risks for death in 30 days or 1 year in relation to length of RBC storage were assessed by using 3 independent analytic approaches. All analyses were conducted by using Cox proportional hazards regression.
Regardless of the analytic approach, no association was found between the length of RBC storage and mortality. The difference in 30-day cumulative mortality between patients receiving blood stored for 30 to 42 days and those receiving blood stored for 10 to 19 days was −0.2% (95% CI, −0.5% to 0.1%). Even among patients who received more than 6 units of RBCs stored for 30 days or longer, the hazard ratio of death was 1.00 (CI, 0.96 to 1.05) compared with those who received no such units.
Observational study; risk of confounding by indication.
Consistent with previous randomized trials, this study found no association between the length of storage of transfused RBCs and patient mortality. Results were homogeneous, with differences in absolute mortality consistently less than 1% among the most extreme exposure categories. These findings suggest that the current practice of storing RBCs for up to 42 days does not need to be changed.
The Swedish Research Council, Swedish Heart–Lung Foundation, Swedish Society for Medical Research, Strategic Research Program in Epidemiology at Karolinska Institutet, and Danish Council for Independent Research.
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